Yoshioka Nori, Deguchi Matsuo, Hagiya Hideharu, Kagita Masanori, Tsukamoto Hiroko, Takao Miyuki, Yoshida Hisao, Yamamoto Norihisa, Akeda Yukihiro, Nabetani Yoshiko, Maeda Ikuhiro, Hidaka Yoh, Tomono Kazunori
Division of Infection Control and Prevention, Osaka University Hospital, Suita, Osaka, Japan.
Laboratory for Clinical Investigation, Osaka University Hospital, Suita, Osaka, Japan.
PLoS One. 2017 Nov 9;12(11):e0187661. doi: 10.1371/journal.pone.0187661. eCollection 2017.
Health care workers (HCWs) are frequently exposed to hepatitis B virus (HBV) infection. The efficacy and safety of immunization with the hepatitis B (HB) vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.
This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs) titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years), and long responders (those who retained positive anti-HBs levels for 3 years and more). We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.
From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229), 54.5% after two doses (n = 11), and 4.2% after a single dose (n = 24). Of 213 primary responders, the anti-HBs levels of 95 participants (44.6%) fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.
Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective, large-scale study is warranted to support our findings.
医护人员经常面临感染乙型肝炎病毒（HBV）的风险。乙肝（HB）疫苗免疫接种的有效性和安全性已得到充分认可，但对于二次疫苗应答失败的人群，免疫的持久性以及是否需要加强剂量仍存在争议。
这是一项在日本大阪大学医院进行的回顾性队列研究。我们对之前未接种疫苗的医护人员接种疫苗后，每年检测其抗-HB表面抗原（抗-HBs）抗体滴度。初次应答者根据其血清阳性持续时间分为短期应答者（抗-HBs滴度在3年内降至阴性范围的人）和长期应答者（抗-HBs水平保持阳性3年及以上的人）。我们对短期应答者进行单剂量或3剂次加强免疫，对长期应答者当其滴度降至保护水平以下时进行单剂次加强免疫，并在此后一段时间内检测其血清保护率。
2001年至2012年，收集了264名医护人员的数据，中位年龄为25.3岁。三剂次接种后抗-HBs阳性率为93.0%（n = 229），两剂次接种后为54.5%（n = 11），单剂次接种后为4.2%（n = 24）。在213名初次应答者中，95名参与者（44.6%）的抗-HBs水平降至保护水平以下，其中包括46名短期应答者和49名长期应答者。初次接种疫苗后初始抗-HBs滴度较高的医护人员血清阳性持续时间明显更长。对于短期应答者，3剂次加强免疫比单剂次加强免疫诱导的抗-HBs阳性持续时间更长，而对于长期应答者，仅单剂次加强免疫就能诱导抗-HBs阳性持续时间延长。
我们的初步数据表明，根据初次应答持续时间区分乙肝疫苗应答者可能有助于有效维持抗-HBs的保护水平。有必要进行一项随机、前瞻性、大规模研究来支持我们的发现。
